Glutaredoxin1

Glutaredoxin-1 (GLRX1) is a small cytosolic enzyme of the thioredoxin-fold superfamily that participates in cellular redox homeostasis by catalyzing reversible glutathionylation and deglutathionylation reactions. It is one of several glutaredoxins encoded by the GLRX gene family and is widely expressed in human tissues.

GLRX1 carries an active-site motif of cysteine residues (CPYC) that enables a dithiol mechanism. During catalysis, the enzyme reduces mixed disulfides between protein thiols and glutathione (protein-SSG), forming a Grx1-glutathione mixed disulfide that is reduced by reduced glutathione (GSH) to release the restored protein and generate GSSG. The catalytic cycle is completed as the enzyme is regenerated by glutathione reductase.

Beyond deglutathionylation, GLRX1 participates in redox signaling by maintaining the thiol status of target proteins, thereby influencing diverse cellular processes such as metabolism, transcriptional regulation, and responses to oxidative stress. The enzyme operates within the broader cellular glutathione system to help preserve protein function under challenging redox conditions.

Localization and regulation: GLRX1 is predominantly cytosolic and expressed across many cell types. Its activity and expression are modulated by the cellular redox state and oxidative stress, reflecting its role in preserving thiol redox balance.

Clinical relevance: Altered GLRX1 expression or activity has been linked to oxidative stress–related diseases, including neurodegenerative disorders and cancer. It is studied as a potential biomarker of redox status and as a therapeutic target for modulating protein thiol oxidation.

Evolution and structure: GLRX1 is conserved across eukaryotes and bacteria, reflecting the widespread importance of thiol-disulfide redox chemistry. As a thioredoxin-like enzyme with a CPYC active site, it shares structural features common to the glutaredoxin family.